The objective of this research project is to elucidate the photochemical and photobiological mechanisms whereby light (UVA and visible radiation) alone or in the presence of endogenous or exogenous photosensitizers exerts either toxic or therapeutic effects. We have shown that UVA has carcinogenic potential in human keratinocytes and that the decreased PTEN expression resulted in increased PI3K/AKT signaling and may contribute to apoptotic resistance and malignant transformation. We have identified the skin lipid cholesta-5,7,9(11)-trien-3 beta-ol (9-DDHC) as the putative agent responsible for UVA-induced skin photosensitivity in Smith-Lemli-Opitz syndrome patients. 9-DDHC generates singlet oxygen and superoxide upon UVA irradiation, is phototoxic to keratinocytes and is found in higher concentrations in plasma from UVA sensitive patients. Fullerol [C60(OH)24], a water soluble fullerene, is cytotoxic and phototoxic to human retinal pigment epithelial (hRPE) cells